The invention relates generally to monoclonal antibodies specific for a neoplasia marker, specifically NADH:protein disulfide reductase, to cell lines producing those neoplastic marker-specific monoclonal antibodies and immunological assays and to diagnostic methods using those monoclonal antibodies and to substantially purified NADH:protein disulfide reductase which is characteristic of transformed cells and/or neoplastic cells or tissue. Because the antibodies specifically prevent the growth of cancer cells, induce apoptotic cell death of cancer cells, without effect on normal cells, the described monoclonal antibodies are useful for inhibiting cancer cell growth and for treating a neoplastic condition.
Our laboratory has described an activity of the HeLa cell plasma membrane that catalyzes the reduction of protein disulfide bonds at the expense of NADH. Measured as an NADH oxidase or NADH:protein disulfide reductase (PDR), the protein in the absence of NADH exhibits a protein disulfide-thiol interchange (TIP) activity. In HeLa cells the ability of plasma membrane vesicles to oxidizes NADH is partially inhibited by the quinone site inhibitor capsaicin (8-methyl-N-vanillyl-6-noneamide) and the antitumor sulfonylurea LY181984. The latter appears to correspond to a 34 kD sulfonylurea binding protein that is exposed at the external surface of the cells and eventually shed into culture media [Wilkinson et al. (1996) Arch. Biochem. Biophys. 336:275-282]. A corresponding capsaicin-[Morré et al. (1997) Arch. Biochem. Biophys. 342:224-230] or sulfonylurea-[Morré and Reust (1997) J. Biomemb. Bioenerg. 29:281-289] inhibited activity is found in sera of cancer patients. Plasma membranes isolated from non-transformed cells or sera from healthy individuals appear to lack entirely the drug inhibited activity [Morré et al. (1995) Proc. Natl. Acad. Sci. USA 92:1831-1835]. Whereas plasma membrane vesicles isolated from both normal and transformed cells exhibit an NADH oxidase activity, only the NADH oxidase activity of plasma membrane vesicles from transformed cells and the shed form from sera of cancer patients are inhibited by capsaicin and the antitumor sulfonylurea.